8-72023917-G-A

Variant names:

• chr8-72023917-G-A
• rs180680340
• NM_007332.3:c.3052-6C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_007332.3(TRPA1):​c.3052-6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000996 in 1,551,724 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (5 hom., cov: 33)
  • Exomes 𝑓: 0.00072 (5 hom.)
• Consequence: TRPA1 NM_007332.3 splice_region, intron
• Scores: Splicing: ADA: 0.000009181
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.814
• Publications: 2 publications found

Genes affected

TRPA1 (HGNC:497): (transient receptor potential cation channel subfamily A member 1) The structure of the protein encoded by this gene is highly related to both the protein ankyrin and transmembrane proteins. The specific function of this protein has not yet been determined; however, studies indicate the function may involve a role in signal transduction and growth control. [provided by RefSeq, Jul 2008]

MSC-AS1 (HGNC:48724): (MSC antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 8-72023917-G-A is Benign according to our data. Variant chr8-72023917-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3025034.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 539 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007332.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPA1	NM_007332.3	MANE Select	c.3052-6C>T		splice_region intron	N/A	NP_015628.2	O75762
	MSC-AS1	NR_033651.1		n.434-28622G>A		intron	N/A
	MSC-AS1	NR_033652.1		n.1029-28622G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPA1	ENST00000262209.5	TSL:1 MANE Select	c.3052-6C>T		splice_region intron	N/A	ENSP00000262209.4	O75762
	MSC-AS1	ENST00000457356.9	TSL:1	n.511-28622G>A		intron	N/A
	TRPA1	ENST00000859810.1		c.3052-6C>T		splice_region intron	N/A	ENSP00000529869.1

Frequencies

GnomAD3 genomes AF: 0.00355 AC: 540 AN: 152062 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.0121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000983

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.00127 AC: 315 AN: 248706 AF XY: 0.00104

Gnomad AFR exome AF: 0.0139

Gnomad AMR exome AF: 0.00117

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000218

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.000356

Gnomad OTH exome AF: 0.000330

GnomAD4 exome AF: 0.000719 AC: 1006 AN: 1399544 Hom.: 5 Cov.: 24 AF XY: 0.000619 AC XY: 433 AN XY: 699602

African (AFR) AF: 0.0117 AC: 380 AN: 32480

American (AMR) AF: 0.00146 AC: 65 AN: 44412

Ashkenazi Jewish (ASJ) AF: 0.0000391 AC: 1 AN: 25584

East Asian (EAS) AF: 0.000640 AC: 25 AN: 39086

South Asian (SAS) AF: 0.000201 AC: 17 AN: 84370

European-Finnish (FIN) AF: 0.0000376 AC: 2 AN: 53242

Middle Eastern (MID) AF: 0.00125 AC: 7 AN: 5586

European-Non Finnish (NFE) AF: 0.000428 AC: 452 AN: 1056734

Other (OTH) AF: 0.000982 AC: 57 AN: 58050

GnomAD4 genome AF: 0.00354 AC: 539 AN: 152180 Hom.: 5 Cov.: 33 AF XY: 0.00351 AC XY: 261 AN XY: 74398

African (AFR) AF: 0.0120 AC: 498 AN: 41504

American (AMR) AF: 0.000981 AC: 15 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 67994

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00239 Hom.: 1

Bravo AF: 0.00418

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000356

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	TRPA1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	14
DANN	Benign	0.58
PhyloP100		0.81
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0000092
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.41		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.41		Position offset: -44
DS_AL_spliceai		0.24		Position offset: -6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs180680340; hg19: chr8-72936152;